Nitric acid oxidation has been employed for many years to convert carbohydrates to acids. See W. N. Haworth and W. G. M. Jones, J. Chem Soc., 1944, pp 66-67. See also J. Stanek, M. Cerney, J. Kocourek and J Pacak, The Monosaccharides, Academic Press, New York, 1963, p. 744 and references 3-41 therein. In the nitric acid oxidation of many compounds, residual nitric acid remains in the oxidation product. In order to isolate the desired oxidation product, it is generally necessary to remove this residual nitric acid. This is particularly true in the nitric acid oxidation of alcoholic compounds such as carbohydrates, although some exceptions exist (notably the crystallization of highly insoluble galactaric acid directly from the oxidation of lactose or other galactose containing saccharides). Nitric acid oxidation of carbohydrates, such as the oxidation of the aldoses "glucose," "xylose" and "mannose" to the desired aldaric acid products "glucaric acid," "xylaric acid" and "mannaric acid," requires that residual nitric acid be at least partially removed in order to isolate the desired oxidation product. A variety of methods for removing nitric acid have been proposed.
For example, the isolation of an aldaric acid can be accomplished by neutralizing the aldaric acid and the residual nitric acid to form inorganic and organic salts that are easily separated. In one well known process of this type, glucaric acid is isolated as a monopotassium salt. See U.S. Pat. No. 2,436,659 issued to Mehltretter. A more recent procedure of this type involves treating an aldaric acid and residual nitric acid with a base, such as potassium hydroxide, to form an aldaric acid salt and an inorganic nitrate, respectively. Subsequently, the salts are separated by a chromatographic procedure. See U.S. Pat. No. 5,599,977 issued to Kiely et al. Regeneration of the aldaric acid in a neutralization process requires acidification of the aldaric acid salt with a strong acid.
These processes are not advantageous since the neutralization and acidification processes are complicated, economically burdensome and time consuming. In addition, it is necessary to dispose of the residual nitrates generated by these processes or further treat the nitrates to form a useful product. On a large commercial scale, it would be desirable to utilize fewer reagents and generate less wasteful by-products.
A second technique for removing residual nitric acid from oxidation reaction products requires repeated concentration steps wherein fresh quantities of water are added to the product between each step. Nitric acid (68%) forms a negative azeotrope with water (32%) that has a boiling point of 120.5.degree. C. Nitric acid is removed by boiling off the azeotrope. However, removal of nitric acid from the reaction mixture by this technique is difficult due to the relatively high boiling point of the nitric acid/water azeotrope.
A third technique for removing residual nitric acid from oxidation reaction products involves the addition of large volumes of 2-propanol to destroy the excess nitric acid followed by water dilution and concentration of the product. See C. E. Cantrell, D. E. Kiely, G. J. Abruscato and J. M Riordan, .delta.-Dicarbonyl Sugars. 5. A Novel Synthesis of a Branched-Chain Cyclitol, J. Org. Chem., 42, 3562 (1977). This process requires consumption of 2-propanol and then isolation of acetone and any other residuals. In addition, further treatment with water followed by hydrogen chloride is required and these compounds must then be removed from the desired product. In short, the process requires too many steps to be economically viable. For aldaric acids such as glucaric acid, this process is coupled with a neutralization process such as the ones described above.
There is, therefore, a need in the art for a simpler and more economic means of separating nitric acid from oxidation reaction products. For example, the aldaric acid "glucaric acid" is not manufactured on an industrial scale because there is no economic process for synthesizing and isolating glucaric acid. See H. Roper, Selective Oxidation of Glucose, Starch/Starke, 42, p. 346 (1990). If a more economical means of removing nitric acid could be found, glucaric acid could be produced from glucose which is readily and cheaply obtained by hydrolyzing common compounds such as starch.
The availability of glucaric acid, and other aldaric acids, on an industrial scale is desirable for use in pharmaceutical preparations, as food acids, and as biodegradable additives to polymeric resins and plastics. Improvements in the preparation and isolation of aldaric acids would also positively impact virtually any process wherein an oxidation product is formed by nitric acid oxidation.